PROJECT SUMMARY Ischemic heart disease affects ~15 million Americans and accounts for ~2,150 deaths every day. The ability to develop multifunctional implants for local delivery of therapeutic agents holds great potential for the treatment of myocardial infarction (MI), which remains challenging today. The objective of this project is to develop a novel cardiac patch with two primary functions of promoting both angiogenesis and anti-inflammation. Compelling preliminary results have been collected, showing that nucleic acid aptamers can be incorporated into hydrogels with the capability of sequestering and releasing therapeutic agents. Based on the compelling results, this project is developed with three specific aims including 1) development of aptamer-functionalized cardiac patches for controlled release of angiogenic factors, 2) evaluation of the functionality of the patches in the promotion of therapeutic angiogenesis and MI treatment, and 3) evaluation of therapeutic angiogenesis and anti-inflammation for synergistic MI treatment. It is anticipated that aptamer-functionalized patches would stably sequester therapeutic proteins and release them in a sustained manner; and that co-delivery of multiple signaling molecules would lead to synergistic MI treatment. The success of this project holds great potential to open a new avenue of developing cardiac implants for the treatment of patients with ischemic heart disease.